Immunogenicity

Immunogenicity is the ability that therapeutic proteins have in generating antibodies against themselves, since they contain unique sequences that can elicit an immune response. Clinical trials with Remicade showed that 10-51 % of treated patients developed anti-drug antibodies (ADA) against Remicade (Vincent 2013). The anti-Remicade antibodies were analyzed by ELISA method which measure binding ADA, and cannot determine whether these factors have functional significance, i.e. if ADA neutralizes the effect of the drug. Furthermore, assays for detection of ADA are often limited by high drug concentration in blood and it is important to test samples with as low drug concentrations as possible. The drug labels do not explain if drug levels were accounted for when testing for immunogenicity in the clinical trials for the different TNF inhibitors.

Today, authorities require estimations of immunogenicity in the clinical trial programs (Phase I through Phase IV) for new biological drugs (EMA 2007 and 2012 and the FDA draft 2009). According to EMA and FDA, tests for NAbs with a biological activity assay should be included where it is relevant.

Due to the growing concern of immunogenicity, it has become more and more common that TNF blockers are given in combination with MTX since this is considered to reduce or delay development of anti-drug antibodies (Jani 2013).